托里消毒散调控TLR4/Myd88/NF-κB通路和NLRP3炎性小体抑制对5-Fu所致的CID小鼠肠道损伤研究  

Tuoli Xiaodu Powder inhibited 5-fluorouracil-induced CID mice intestinal injury by regulating TLR4/Myd88/NF-κB pathway and inhibiting NLRP3 inflammasome

作　　者：吴勇俊 蒋凌 蒋婉柔 张万翼 黄洪婕[1] 祝朝富 WU Yongjun;JIANG Ling;JIANG Wanrou;ZHANG wanyi;HUANG Hongjie;ZHU Chaofu(Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China)

机构地区：[1]成都中医药大学附属医院,成都610075 [2]成都中医药大学,成都610075

出　　处：《天津中医药》2024年第11期1431-1437,共7页Tianjin Journal of Traditional Chinese Medicine

基　　金：四川省科技计划项目(2022NSFSC0748)。

摘　　要：[目的]化疗相关性腹泻(CID)是5-氟尿嘧啶(5-Fu)治疗最常见的不良反应。本研究旨在研究托里消毒散对CID的潜在保护作用,并探讨其可能的机制。[方法]将5-Fu致CID模型小鼠随机分为对照组、空白组、CID模型组、阳性药物(洛哌丁胺)组、托里消毒散-散低剂量组、托里消毒散-中剂量组和托里消毒散-高剂量组。评估各组小鼠腹泻程度、肿瘤生长、肠屏障损伤、肠道炎症和Toll样受体4(TLR4)/骨髓分化主要反应蛋白88(Myd88)/核因子κB(NF-κB)通路活性和NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体活化水平。[结果]研究表明,托里消毒散能明显抑制5-Fu诱导的CID小鼠腹泻和肿瘤生长。苏木精-伊红(HE)染色结果显示,与CID模型组相比,托里消毒散能改善5-Fu诱导的CID小鼠肠黏膜损伤。此外,与CID模型组相比,托里消毒散导致CID小鼠肠道内炎症因子白细胞介素(IL)-1β、IL-8、IL-6以及肿瘤坏死因子(TNF)-α的表达降低,NLRP3水平也明显下降。[结论]托里消毒散通过抑制CID小鼠肠道TLR4/Myd88/NF-κB通路活性和NLRP3炎性小体活化水平减轻5-Fu所致CID小鼠的肠道损伤,为CID治疗提供了一种新的方法。[Objective]Chemotherapy-induced diarrhea(CID)is a common adverse reaction in cancer patients treated with 5-fluorouracil(5-Fu).This study aimed to investigate the potential protective effect of Tuoli Xiaodu Powder on CID and explore its possible mechanism.[Methods]The 5-Fu-induced CID mice were randomly divided into control group,blank group,CID model group,positive drug(loperamide)group,Tuoli Xiaodu Powder-low dose group,Tuoli Xiaodu Powder-medium dose group and Tuoli Xiaodu Powder-high dose group.The severity of diarrhea,tumor growth,intestinal barrier damage,intestinal inflammation,Toll-like receptor 4(TLR4)/Myeloid differentiation primary response protein 88(Myd88)/Nuclear factor kappa-B(NF-κB)pathway activity and NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation were evaluated.[Results]The results showed that Tuoli Xiaodu Powder significantly inhibited the diarrhea and tumor growth of 5-Fu-induced CID mice.Hematoxylin and Eosin staining(HE)outcome showed that compared with the CID model group,Tuoli Xiaodu Powder improved the intestinal mucosal injury induced by 5-Fu in CID mice.In addition,compared with the CID model group,Tuoli Xiaodu Powder reduced the expression of inflammatory factors interleukin(IL)-1β,IL-8,IL-6,and tumor necrosis factor(TNF)-αin the intestinal tract of CID mice,and the level of NLRP3 was also significantly decreased.[Conclusion]Tuoli Xiaodu Powder can reduce the intestinal injury of CID mice induced by 5-FU by inhibiting the activity of TLR4/Myd88/NF-κB pathway and the activation level of NLRP3 inflammasome in the intestinal tract of CID mice.These findings provide a new therapeutic strategy for the treatment of 5-Fu-induced CID in cancer patients.

关 键 词：托里消毒散 TLR4/Myd88/NF-κB通路 NLRP3炎性小体 化疗相关性腹泻 

分 类 号：R285.5[医药卫生—中药学]